Six months after the FDA withheld an internal finding that anti-depressant medications were associated with an increased risk of suicide among children, a second staff analysis has arrived at the same conclusion.
The agency has refused to publicly disclose either report, despite growing pressure from critics and Congress. Agency officials say they don’t plan to discuss the data until a scheduled meeting in September, which would come nine months after British authorities warned physicians not to prescribe Paxil, Zoloft, Celexa and similar drugs to depressed children, and more than a year after the first concerns emerged.
The new analysis has renewed critics’ complaints that the FDA is moving too slowly to address the concerns about suicide.
One leading expert who reviewed the two internal analyses said they had changed his thinking about the risks. “I didn’t have access to the proprietary data” reflected in the FDA analyses, said Steven Hyman, former director of the National Institute of Mental Health, who initially felt British regulators had overreacted. Hyman reviewed the analyses at the request of the Washington Post.
“Now I would say from the data in front of me, with the exception of Prozac, there is concern about the risk-benefit ratio of antidepressants in children,” said Hyman.
FDA officials have declined to release the new analysis, first reported by the Wall Street Journal, and said they were still reviewing the information. “It would be premature to discuss any conclusions and results,” said spokeswoman Kathleen Quinn. “Other people are going to have an opinion about it, but we are still reviewing it.”
The new analysis comes amid growing concerns that crucial information about the safety and effectiveness of the drugs has been withheld from public scrutiny. Two-thirds of the trials conducted by drug manufacturers found that the medications performed no better than sugar pills, but details of the negative trials were kept from doctors and parents.
Joseph Glenmullen, a Harvard psychiatrist and author of “Prozac Backlash,” a book about the side effects of antidepressants, said one company, Wyeth, had warned doctors not to prescribe its anti-depressant Effexor for children: “The companies are coming to this conclusion, and the British came to this conclusion, and the Canadians and the rest of Europe and the FDA’s own reviewer have come to this conclusion; why have they dragged their feet for over a year?”
The new “interim review” by FDA medical reviewer Tarek Hammad is a compilation of data that has no narrative or interpretation. But both Hyman and Glenmullen said it showed an increased risk for children taking the drugs similar to that found in February by another FDA scientist, Andrew Mosholder.
Hammad’s review found that compared to depressed children who got sugar pills, children who got antidepressants had 1.78 times the risk of making a suicide attempt or “making preparatory actions towards imminent suicidal behavior.”
Mosholder found that children getting antidepressants had 1.9 times the risk of “serious suicide-related events.”
Multiple congressional investigations are under way into the controversy. The chairman of the Senate Finance Committee, Charles Grassley, R-Iowa, said in a statement Monday: “It’s been almost nine months since British regulators issued new recommendations, and it’s been six months since Dr. Mosholder made his determinations. Now, given this new information, it’s fair to ask if the Food and Drug Administration is taking too much time to draw a conclusion.”
The FDA’s associate director for medical policy, Robert Temple, said in an April interview that officials believed a second analysis might provide a different answer than Mosholder’s: “Andy thinks the results are unlikely to change from this analysis, and we are not so sure of that.”
Temple said the agency had decided to withhold Mosholder’s findings because “we didn’t think it was time to present a conclusion about a study because we as an agency didn’t want to present it… in the absence of all the data; you want to be careful about reaching premature conclusions.”
Agency officials said then that they were concerned about whether the companies had classified suicidal cases properly, and referred the question to Columbia University scientists. But in a Feb. 18 memo, Mosholder warned that the new analysis would waste time: “In my view, it is unlikely that the new information will alter the basic finding of an association of serious suicide-related events with active treatment.”
Given the risks, he urged the agency to take the interim step of officially discouraging the use of antidepressants other than Prozac for children. The FDA declined to do so but called for stronger warning labels to remind doctors to be vigilant about suicide for over a decade, the agency has said that depression, not antidepressants, causes suicidal behavior.